HIVNET 012

A Phase IIB Trial to Determine the Efficacy of Oral AZT and the Efficacy of Oral Nevirapine for the Prevention of Vertical Transmission of HIV-1 Infection in Pregnant Ugandan Women and Their Neonates

Study Summary

What was HIVNET 012?

HIVNET 012 was a randomized clinical trial to evaluate the efficacy of two short-course antiretroviral drug regimens for the prevention of HIV transmission from infected mothers to their babies. The overall goal of the study was to identify a safe, effective means of preventing mother-to-infant HIV transmission that would be applicable and affordable in resource-limited settings.

Who participated in the study?

HIV-1 infected Ugandan women and their infants. The original study size was 1,500 mother-infant pairs. 642 evaluable mother/infant pairs were enrolled in the interim (phase IIB) study.

What happened during the study?

This study was originally designed as a randomized, double-blind, three-arm placebo-controlled trial to determine the efficacy of a short course of nevirapine and the efficacy of a short course of AZT for the prevention of mother to infant HIV transmission, with the goal of finding a safe, effective means of preventing mother-to-infant transmission that would be applicable and affordable in resource-limited countries. Soon after the study was initiated, results of another study were released which led to the placebo arm being dropped. Enrollment into the two active agent arms of the study (open-label Phase IIB component) was continued to provide preliminary screening data on the efficacy of the two antiretroviral regimens in an effort to select one of the two for inclusion in a re-designed efficacy trial comparing the selected regimen with an appropriate control.

Results

This landmark study found that a short intrapartum/neonatal regimen of nevirapine given to the mother at the onset of labor and to the infant within 72 hours of life reduced the risk of perinatal HIV transmission among breastfeeding women in Uganda by 47% at 14-16 weeks and by 41% at 18 months compared to a short intrapartum/neonatal regimen of AZT.

Study Details

Protocol Status: Concluded
Study Purpose:

To determine the efficacy of oral AZT and the efficacy of oral nevirapine for the prevention of vertical transmission of HIV-1 infection from pregnant Ugandan women to their infants.

Study Design:

This study was originally designed as a randomized, double-blind, three-arm placebo-controlled trial to determine the efficacy of a short course of Nevirapine and the efficacy of a short course of AZT for the prevention of mother to infant HIV transmission, with the goal of finding a safe, effective means of preventing mother-to-infant transmission that would be applicable and affordable in resource-limited countries. Soon after the study was initiated, results of another study were released which led to the placebo arm being dropped. Enrollment into the two active agent arms of the study (open-label Phase IIB component) was continued to provide preliminary screening data on the efficacy of the two antiretroviral regimens in an effort to select one of the two for inclusion in a re-designed efficacy trial comparing the selected regimen with an appropriate control.

Study Population:

HIV-1 infected Ugandan women and their neonates

Study Size:

The original study size was 1500 mother-infant pairs. 642 evaluable mother/infant pairs were enrolled in the interim (phase IIB) study.

Study Duration:

Enrollment took place over 18 months. The original study design included 18 months of follow-up for infants and 6 weeks of follow-up for mothers; follow-up was later extended to five years.

Treatment Regimen:

After the placebo arm was dropped, mother-infant pairs were randomized in a 1:1 ratio to one of two arms. In one arm mothers received a single oral 200 mg dose of NVP at onset of labor and their infants received a single oral 2 mg/kg dose of NVP within 72 hours or birth. In the other arm, mothers received a single oral 600 mg bolus dose of AZT at onset of labor, then 300 mg of AZT every 3 hours until delivery and their infants received an oral 4 mg/kg dose of AZT once a day for 7 days.

Primary Objectives:

To determine the rate of HIV-1 infection in infants born to study participants in each arm of the study as determined by a positive qualitative plasma HIV-1 RNA result confirmed at the next visit by a positive culture or quantitative plasma RNA level on a different specimen for infants < 18 months of age.
To determine the proportion of infants who are alive and free of HIV at 18 months. To evaluate the safety/tolerance of oral NVP and oral AZT given to pregnant Ugandan women during labor and their neonates during the first week of life.

Secondary Objectives:

Rates of disease progression in the infected infants in each arm
Infant survival in each arm (mortality, regardless of HIV infection)
Relationship of maternal plasma RNA levels at delivery with risk of perinatal transmission
The rate of infant death or HIV-1 infection

Key Study Personnel

Melissa Allen, CORE Protocol Specialist
Lynda Marie Emel, SDMC Protocol Specialist
J. Brooks Jackson, Protocol Chair